Visionary Leadership, Innovation and Clinical Research Transform the Future of Ophthalmology

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Dr. Daniel Simon: Hello everyone. Thank you for listening to another Science@UH episode. I am your host, Dr. Dan Simon and today I am happy to be joined by Dr. Jonathan Lass, the Charles I Thomas Professor in the Department of Ophthalmology and Visual Sciences at Case Western Reserve University, distinguished attending surgeon of the Center for Anterior Segment Diseases and Surgery in the University Hospitals Eye Institute and Director of the University Hospitals Eye Image Analysis Reading Centers. Welcome, Jonathan.

Dr. Jonathan Lass: Thank you, Dan.

Dr. Daniel Simon: So Jonathan, first I want to start by congratulating you, and it's really inspiring, on your recent celebration of the 45th anniversary of you being at University Hospitals. Really, congratulations! You joined you as medical staff in 1979 and served as the Chair of the Department of Ophthalmology from 1993 to 2013. And you have many milestones throughout your career, one of them of course, is the formation of the Eye Image Analysis Reading Centers in 1989. One for the cornea and one for the retina. Can you tell us a little bit about... what exactly is a reading center and what role does it play in multicenter national and international trials, both federal trials and industry sponsored trials? What are the kinds of things that have led to therapeutic approvals that your doing here.

Dr. Jonathan Lass: Well, the reading center started because of my interest in the corneal endothelium, this is the back cell layer of the cornea that keeps the cornea dehydrated. And there is an instrument called the specular microscope that allows you to look at these cells in vivo and then follow any changes in those cells as you get older or after a procedure or after.  So, it really lended itself by having these images to ultimately establishing a reading center that would allow for a very controlled, reproducible way of measuring the density of these cells, the shape and size of these cells. And so it started with one person at a desktop, and we now have over 30 employees doing image analysis work, both on the cornea and similarly on images of the retina. So this really lends itself to safety studies that many of the companies as they're trying to develop new drugs or devices or new procedures and the FDA is requiring these safety studies, they turn to a reading center for a more reproducible way of getting that data. So we're very much involved in, even as early as, you know, phase one, but most of them are phase two or three studies where the company is being required to do this testing. We are doing some efficacy studies to both of the cornea, but also for the retina, which includes studies on new treatments for macular degeneration or diabetic retinopathy. Our federal studies also have been exploring important questions around eye banking and transplantation in terms of different parameters that could affect the outcome of the transplant. So we've looked at the age of the donor, that was the first corner donor study, which was 20 years ago. Then we looked at how long the cornea is preserved before the surgery and how long you can preserve it for while it's still good. And now we're looking at the effect of diabetes in the donor and also on their recipient on those cells and on those transplants.

Dr. Daniel Simon: You know, it's really amazing. Jonathan, to think about the fact that Cleveland is a real hub for this clinical research for new therapeutics for the eye. Tell me, are you using computer assisted imaging analysis, and AI now in interpretation of these images or is it still really coming down to individual people looking at these images?

Dr. Jonathan Lass: We are actively working with the biomedical engineering group and Dave Wilson, that Farouk (Orge) is also, I know you interviewed Faruk earlier. We're working with Dave as well in terms of an automated approach to analyzing those cells and actually, the timing is very good. We just published with their group in one of the top-level journals called TBST, it's an orvo journal...last week. And it could really revolutionize the analysis of those cells... where normally, it would take 10-15 minutes to analyze that image, here you can have a much more comprehensive analysis of those same images and look at many more cells in a much more reproducible way. So that's where it's headed.

Dr. Daniel Simon: Yeah, that's really terrific, Jonathan. Your expertise obviously lies in the cornea, corneal imaging analysis and its potential role in corneal transplantation. Tell our listeners a little bit about what is the leading indication for corneal transplantation. And tell us a little bit about what you've done through both the national eye institutes, RCT's in cornea donor study, the cornea preservation study and now the work that you're doing in the diabetes, endothelial keratoplasty study. So why do you need a corneal transplant? Who's getting them? And what's the latest in that space?

Dr. Jonathan Lass: The leading indication for transplants in the United States at least, is a condition called Fuchs dystrophy, where the endothelial cells, those same cells we talked about imaging, they begin to deteriorate as you get older and they actually have this appearance of these expresses, these deposits on the back called guttata and eventually the cornea can swell. So, I've been looking at that disease in many different ways. With these transplant studies that I talked about, including most recently this...although we're looking at the effect of the diabetes on the corneal transplants... we're also looking at Fuchs dystrophy because 95% of all the patients in our trial...where we've just completed enrollment of nearly 1100 patients at 28 clinical sites and supported by 13 eye banks with that trial, supported by the National Institute. Anyway, most of those patients have few Fuchs dystrophy. So you know, we're not only going to learn about the effect of diabetes, we're going to also be coming up with the best ways to treat this disease with this surgery. The reading center is also looking at new medical treatments for Fuchs dystrophy, and so we're, it all kind of comes together with the clinical trials with the reading center. And I'm also working closely with Dr. Iyengar in the population quantitative health sciences on the genetics of Fuchs dystrophy. So, we just actually reported working with the VA and the Million-Veteran Program.  And we also published a few years ago, in Nature, looking at new genes that could relate to this complex genetic disorder which is Fuchs dystrophy.

Dr. Daniel Simon: So how many corneal transplants are there in the US in a year?

Dr. Jonathan Lass: It's the most common reason for transplants. It's nearly 50,000 a year.

Dr. Daniel Simon: Wow, that's incredible. You know, as a cardiologist, we're lucky to do 3000 plus transplants in the US, and it's been pretty flat.

Dr. Jonathan Lass: And I'm very active with our eye bank here in Cleveland, and which it's called Eversight. And I'm on their board, so yes, I mean to provide that gift of sight to all those individuals is inspiring.

Dr. Daniel Simon: Yeah, that's really amazing. So Jonathan, in recent times. We now talk a lot about team science and team sciences multidisciplinary, interprofessional, combining MD's, PhD's and others. And you know way back, I guess in 1996, with the support of CWRU Dean, Nathan Burger and Dr. Hunt Willard, who at the time was the VP for Research at UH,  you founded the Visual Science Research Center, which has really flourished, with you, the first PI of the P30 core grant back in 1997. 27 years later, Dr. Pikuleva is now the PI of that grant. Tell us about the importance of team science. What's the secret sauce of it? What have you been able to do through the Visual Science Center in this team-based way?

Dr. Jonathan Lass: I’ve just become chairman like three years before and I only, at that time, had one basic scientist in ophthalmology. And I said how the heck am I going to build this vision program? So, I actually looked up who else is doing vision research both at UH and at Case. And you know, we had enough investigators in all these different basic science departments and neuroscience and biochemistry and pathology, in medicine, that we had a story here. We had a group and the core grant was the way of bringing that whole group together. And so Nate and Hunt were very supportive and so we were able to create a story about 3 or 4 different modules, a laboratories that could support investigators and amplify their work. And then collaboration started coming. We started getting not just RO1s, but larger center grants. And we had three or four of those. So, bringing people together with different disciplines really led to the growth of both of within ophthalmology, but in these other departments. And we still... at one time we had at least 34 different NEI...we still have a significant program. We've had a few changes; we're rebuilding, but still the core grant...you know had we've had continuous funding with that core grant since 1997. And the VSRC still remains very strong and we continue our building. It's constantly changing. We're fortunate to have Dr. Irina Pikuleav leading as our Center Director now.

Dr. Daniel Simon: That's really terrific. So one of the questions that I wanted to ask you about does affect my family, so I'll give that disclosure, is that of age-related macular degeneration. Tell us a little bit about what's new in that space. We're starting to see commercials on TV for treatments for age-related macular degeneration. Tell our listeners a little bit about that, is ther hope.

Dr. Jonathan Lass: I think if you speak to anyone who's...my father went blind from macular degeneration... he was driving up to the age of 93 and eventually developed the wet form of the macular degeneration and went blind...and this was before any of the anti-VEGF, antivascular endothelial growth factor medications were available. But now, there's just been a tremendous of these anti-VEGF drugs, which had been around for 10 years, and they used to have to give these injections once a month. But now they're coming up with new delivery systems to deliver these drugs less frequently. So that's for the wet form. So there have been huge advantages that can stabilize so it doesn't progress to the level of what happened with my father and even potentially have them that allowed to keep driving.

Now the latest area is related to the dry form or the gyrate form of that which is geographic atrophy. So there's a new strategy surrounding that and there are new medications there.  So there's tremendous advances in both, particularly first in the wet form and now there are advances going on in the dry form. So there's been, you know, 20 years ago there was no hope. Now there is tremendous promise for the managemen. And our reading centers actually involved in testing the efficacy of these new drugs as they come on the market.

Dr. Daniel Simon: That's really exciting. OK, so now just before we conclude, a little something personal about you. So you're an avid cellist. You're a founding member of the World Doctors Orchestra since 2008. You've organized concerts at Severance Hall and performances in the past two years have been in Amsterdam, Copenhagen, Boston and others. Tell us, how is the music world for Doctor Lass?

Dr. Jonathan Lass: It's just been very exciting. I just organized another concert in Phoenix. It's just a perfect combination of great music and charity and travel all coming together. And the orchestra...they just gave a concert in South Korea last week. I unfortunately, I wasn't able to make it, but we've raised over €2 million for charities around the world, including here in Cleveland for the free clinic in 2009. But it's just amazing how we now have over 2000 doctors from 50 countries involved with this organization. And there's just a tremendous parallel universe of both music and medicine. And in terms of the humanism around it, the working through the collaboration, the joy, and then that you can give that joy to an audience or to a patient. So it's just been a great confluence of all these coming together with this orchestra. For myself..I've actually... the clinical trials that I've done in writing these clinical trial grants...I almost see them like symphonies Because basically I have composed this symphony and my sponsor is a the National Eye Institute. And then I get a great orchestra together, with all these great investigators around the country and we create wonderful music with our clinical trials bringing them all together. So it's sort of an inspiration in many ways of bringing both the science and the music together.

Dr. Daniel Simon: Well, what an inspiration to talk to you today. It's been an honor and a privilege. I'm blessed to have known you and now, Dr. Rhee and his role as Chair of Ophthalmology, it's really one of our very special departments. Thank you so much for taking time to speak with us today, Dr. Lass.